Oxygen‐Independent Supramolecular Nanoplatform for Photothermal‐Thermodynamic Therapy against Periodontal Anaerobic Infections

Radical-based nanotherapeutics hold great promise for the treatment of periodontitis. However, the hypoxic/anaerobic microenvironment within periodontal pockets significantly restricts the antibacterial efficacy and clinical translatability of oxygen-dependent radical therapy. By conjugating gold nanorods (AuNRs) with carboxylatopillar[5]arene (CP5), followed by the loading of 2,2'-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride (AIPH) via host-guest recognition interactions, we develop an oxygen-independent radical delivery nanoplatform (AIPH⊂CP5-AuNR) to overcome the abovementioned barrier. Upon 808 nm near-infrared (NIR) irradiation, AuNRs induce localized photothermal effects that not only disrupt bacterial biofilms via photothermal therapy (PTT) but also trigger the thermal decomposition of AIPH to generate oxygen-independent alkyl radicals, thereby enabling thermodynamic therapy (TDT). Both in vitro and in vivo studies demonstrate that the cascaded PTT/TDT approach effectively eradicates pathogenic biofilms and alleviates periodontitis in rat models. This study not only proposes a novel oxygen-independent therapeutic strategy but also expands the biomedical applications of supramolecular nanomaterials in stimuli-responsive drug delivery.